Spasmodic dysphonia (SD) is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although clinical symptoms of SD are well characterized, the ...pathophysiology of this voice disorder is unknown. We describe here, for the first time to our knowledge, disorder-specific brain abnormalities in SD patients as determined by a combined approach of diffusion tensor imaging (DTI) and
postmortem
histopathology. We used DTI to identify brain changes in SD and to target those brain regions for neuropathological examination. DTI showed rightsided decrease of fractional anisotropy in the genu of the internal capsule and bilateral increase of overall water diffusivity in the white matter along the corticobulbar/corticospinal tract in 20 SD patients compared to 20 healthy subjects. In addition, water diffusivity was bilaterally increased in the lentiform nucleus, ventral thalamus, and cerebellar white and gray matter in SD patients. These brain changes were substantiated with focal histopathological abnormalities presented as a loss of axonal density and myelin content in the right genu of the internal capsule and clusters of mineral depositions containing calcium, phosphorus and iron in the parenchyma and vessel walls of the posterior limb of the internal capsule, putamen, globus pallidus, and cerebellum in the
postmortem
brain tissue from one SD patient compared to three controls. The specificity of these brain abnormalities is confirmed by their localization limited only to the corticobulbar/corticospinal tract and its main input/output structures. We also found positive correlation between the diffusivity changes and clinical symptoms of SD (
r
= 0.509,
p
= 0.037). These brain abnormalities may alter the central control of voluntary voice production and, therefore, may underlie the pathophysiology of SD.
Lesion studies in neurological patients revealed that the inferior motor cortex is indispensable for the voluntary control of the phonatory apparatus. The present study serves to identify ...cortico-cortical connections of the inferior motor cortex in order to find out additional areas possibly involved in voice control. In three anaesthetized rhesus monkeys, the larynx representation of the motor cortex was identified using focal electrical brain stimulation and indirect laryngoscopy. After identification, the larynx area was injected with biotin dextranamine, an anterograde tracer. Seven weeks later, the animals were killed and their brains were histologically processed. Projections were found into the surrounding motorcortex, ventral and dorsal parts of premotor cortex, Broca's area, anterior cingulate gyrus, supplementary motor area, lateral prefrontal cortex, orbital cortex, insula, fronto- and parieto-opercular cortices, primary and secondary somatosensory cortices, parietal cortex, and superior temporal gyrus. A number of these structures have been shown by modern imaging techniques to be active during speech.
According to recent research, selective neuronal vulnerability in Parkinson's disease (PD) results from several phenotypic traits, including calcium-dependent, feed-forward control of mitochondrial ...respiration leading to elevated reactive oxygen species and cytosolic calcium concentration, an extensive axonal arbor, and a reactive neurotransmitter. Therefore, antioxidant therapy is a promising direction in the treatment of PD. In vitro studies have indicated the survival-promoting activity of bacterial melanin (BM) on midbrain dopaminergic neuron cultures. It has been established that BM has a number of protective and anti-inflammatory properties, so there is a high probability of a protective effect of BM in the early stages of PD. In this study, PD was induced through the unilateral intracerebral administration of rotenone followed by bacterial melanin. Tissues (brain, lungs, and small intestine) from the observed groups underwent isolation and purification to extract isoforms of new thermostable superoxide (О
)-producing associates between NADPH-containing lipoprotein (NLP) and NADPH oxidase-Nox (NLP-Nox). The optical absorption spectral characteristics, specific amounts, stationary concentration of the produced О
, and the content of NADPH in the observed associates were determined. The optical absorption spectra of the NLP-Nox isoforms in the visible and UV regions in the experimental groups did not differ from those of the control group. However, compared with the control group, the specific content of the total fractions of NLP-Nox isoforms associated with PD groups was higher, especially in the small intestine. These findings suggest that the described changes may represent a novel mechanism for rotenone-induced PD. Furthermore, bacterial melanin demonstrated antioxidant properties and regulated membrane formation in the brain, lung, and small intestine. This regulation occurred by inhibiting the release of new membrane-bound formations (NLP-Nox associates) from these membranes while simultaneously regulating the steady-state concentration of the formed О
.
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